This competing renewal application proposes to continue the follow-up research on 775 families enrolled in the Center's prospective investigations into the etiology of substance use disorder (SUD). The probands are men with lifetime presence/absence of SUD consequent to use of an illicit drug who have a 10-12 year old biological son or daughter. The biological children of SUD men are assigned to the high average risk (HAR) group whereas offspring of men without SUD, having neither axis 1 disorder (normal) nor SUD psychiatric disorder, are assigned to the low average risk (LAR) groups. These children are currently in varying stages of follow-up evaluation conducted at ages 12-14, 16, 19, and annually thereafter until age 30. We have already shown that we can predict in 10-12 year old youth cannabis use disorder by age 22 with approximately 70% accuracy, thereby substantiating the paradigm, subject recruitment strategy and measurement protocols. Multidisciplinary research is conducted on family members (father, mother, children, step-parents) with the objective of elucidating the genetic, biobehavioral and environmental factors on development of SUD consequent to use of illegal drugs. Research protocols are organized into three thematically connected research modules (Neurogenetics. Developmental Psychopathology, and Translation) linking etiology and prevention. The research components thus align with the NIH Roadmap model such that basic science informs clinical research leading to prevention guided by an understanding of etiology. In addition to module-level research, faculty also participate in 3 centerwide aims: 1) Devise a practical scale to quantify the transmissible liability to SUD; 2) Empirically test a biopsychological theory of SUD etiology focusing on off time maturation leading to psychological dysregulation predisposing to SUD; and, 3) Delineate SUD liability variants within an ontogenetic framework. The Center has the program name Center for Education and Drug Abuse Research (CEDAR). It consists of six components (3 cores & 3 research modules): 1) Science Administration (R. Tarter, Ph.D.), 2) Clinical Core (J. Cornelius, M.D.), 3) Statistics Core (L. Kirisci, Ph.D.), 4) Neurogenetics Module (M. Vanyukov, Ph.D.) 5) Developmental Psychopathology Module (D. Clark, M.D., Ph.D.), and 6) Translation Module (Ty Ridenour, Ph.D.). Vertical and horizontal integration of the Center's components promote collaborative research encompassing multiple disciplines. To date, this research program has supported over 360 publications, 4 books, and 3 special journal issues as well as the training of numerous students, faculty and fellows. Six K awards are currently funded using CEDAR resources.